Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With use of iron histochemistry and immunohistochemistry, regional changes in the appearance of iron, ferritin, transferrin, glial fibrillary acidic protein-positive astrocytes, and activated microglia were examined from 1 to 24 weeks after transient forebrain ischemia (four-vessel occlusion model) in rat brain. Expression of the C3bi receptor and the major histocompatibility complex class II antigen was used to identify microglia. Neuronal death was confirmed by hematoxylin-eosin staining only in pyramidal cells of the hippocampal CA1 region, which is known as the area most vulnerable to ischemia. Perls' reaction with 3,3'-diaminobenzidine intensification revealed iron deposits in the CA1 region after week 4, which gradually increased and formed clusters by week 24. Iron also deposited in layers III-V of the parietal cortex after week 8 and gradually built up as granular deposits in the cytoplasm of pyramidal cells in frontocortical layer V. An increasing astroglial reaction and the appearance of ferritin-immunopositive microglia paralleled the iron accumulation in the hippocampal CA1 region, indicating that iron deposition was probably produced in the process of gliosis. Neither neuronal death nor atrophy was found in the cerebral cortex. Nevertheless, an astroglial and ferritin-immunopositive microglial reaction became evident at week 8 in the parietal cortex. On the other hand, the granular iron deposition in the pyramidal neurons of frontocortical layer V was not accompanied by any glial reaction in the chronic stage of ischemia. Three different types of iron deposition in the chronic phase after transient forebrain ischemia were shown in this study. In view of the neuronal damage caused by iron-catalyzed free radical formation, the late-onset iron deposition may be relevant to the pathogenesis of the chronic brain dysfunction seen at a late stage after cerebral ischemia.
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PMID:Regional differences in late-onset iron deposition, ferritin, transferrin, astrocyte proliferation, and microglial activation after transient forebrain ischemia in rat brain. 786 Jun 55

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery. 788 59

Changes in glial cells were investigated immunohistochemically in the autopsy brains of patients with Binswanger-type infarction and the brains of rats with chronic cerebral hypoperfusion. Activated microglia, which are positive for MHC class II antigen, and GFAP immunoreactive astroglia were 3.1 times and 1.6 times, respectively, more numerous, in Binswanger-type infarction than in normal white matter. Chronic cerebral hypoperfusion after bilateral permanent occlusion of the carotid arteries elicited marked activation of microglia and an increase in astroglia in the medical corpus callosum after 1 day of occlusion, and these findings persisted up to 30 days after the occlusion. A decreased number of transferrin-immunoreactive oligodendroglia and rarefaction of the white matter were noted after 14 days of occlusion. These findings indicate that chronic mild ischemia may lead to rarefaction of the white matter, and that the activation of glial cells, which precedes rarefaction of the white matter, may be involved in the pathogenesis of Binswanger-type infarction.
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PMID:[Changes in glial cells in Binswanger-type infarction]. 794 34

In summary, much evidence supports the formation of toxic oxygen metabolites in ischemic reperfused tissue. Tissues are equipped with both an intracellular and extracellular antioxidant defense system. The defense system can also be divided into enzymatic and nonenzymatic defenses. Important components of a nonenzymatic antioxidant include alpha-tocopherol, ascorbic acid, and beta-carotene as well as other compounds that can react with radicals to form less reactive products such as sulfur-containing amino acids. Extracellular fluid comprises a second line of defense against oxidant injury. These extracellular antioxidants include ceruloplasmin, albumin, transferrin, haptoglobin, and uric acid. The oxidant injury can potentially occur during ischemia and reperfusion due to (1) an excess production of oxygen free radicals, (2) a decrease in antioxidant defenses, or (3) both. Because antioxidants function by removing the toxic oxygen metabolites, they are generally highly effective in reducing ischemia-reperfusion injury.
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PMID:Antioxidant effectiveness in ischemia-reperfusion tissue injury. 801 92

Attenuation of oxidative reperfusion injury in skeletal muscle by the administration of iron-chelating compounds suggests that ischemia-reperfusion is associated with delocalization of iron with subsequent catalysis of hydroxyl radical generation. To test this hypothesis we examined the extent of iron liberation and lipid peroxidation in a well-established model of high-grade partial hindlimb ischemia and reperfusion. Laparotomy was performed on heparinized male Sprague-Dawley rats with isolation of the infrarenal aorta. Resting membrane potential (Em) and conjugated diene content in hindlimb skeletal muscle were determined along with plasma iron concentration and percent saturation of transferrin in five groups of animals. Baseline animals (n = 6) underwent a 30-minute postoperative stabilization period before data collection; Sham ischemia animals (n = 10) underwent aortic exposure without clamping for 120 minutes; ischemia animals (n = 8) underwent aortic clamping for 120 minutes; sham reperfusion animals (n = 8) underwent aortic exposure without clamping for 150 minutes; reperfusion animals (n = 8) underwent aortic clamping for 120 minutes followed by 30 minutes of reperfusion. Iron delocalization occurred during ischemia, as indicated by a significant rise in percent saturation of transferrin over that of the corresponding sham group (35% +/- 2% vs 25% +/- 2%; p < 0.05) and persisted during reperfusion (39% +/- 5% vs 27% +/- 3%; p < 0.05). Depolarization of resting Em was noted during ischemia (-75.7 +/- 1.7 mV vs - 92.6 +/- 0.4 mV in the corresponding sham group; p < 0.01), with only partial repolarization demonstrated after reperfusion (-82.2 +/- 1.7 mV; p < 0.01 vs all other groups).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iron delocalization occurs during ischemia and persists on reoxygenation of skeletal muscle. 808 87

The expression of some genes has been comparatively studied in transplanted rat liver and in liver reperfused after ischemia in situ. Experiments on protein synthesis by tissue slices from cold-stored or transplanted livers show that rat livers that retain a good capacity for protein synthesis during storage undergo a profound impairment in the capacity for protein synthesis during the first hours after transplantation. This recovers in the following hours. There is never any indication of synthesis of stress proteins, and of hsp 70 in particular. The steady-state level of mRNAs for albumin, transferrin, and beta-actin, which are well expressed in reperfused postischemic livers in vivo, are reduced early after transplantation and recover only many hours later. Run-on analysis shows that an early defect in transcription and a partial recovery of this process later on are responsible for these changes. The steady-state levels of the same mRNAs are well maintained in donor livers preserved in University of Wisconsin solution for at least 12 hr, and less satisfactorily in Euro-Collins solution. Results of run-on analysis parallel the data on mRNA levels. The behavior of these mRNAs is, therefore, clearly different in reperfused and transplanted liver. The early stages of liver transplantation seem to be characterized by a depressed capacity of gene expression, without the reactive phenomenon of activation of stress protein genes that occurs in reperfused postischemic livers.
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PMID:Protein synthesis and gene expression in transplanted and postischemic livers. 849 10

Analyzing the distribution pattern of transferrin (Tf) and ferritin, we investigated the changes in iron metabolism related proteins in the process of neuronal death induced by 5 min ischemia. In the control animals, Tf immunoreactivity was localized in the oligodendrocytes. Ferritin was distributed in both neurons and gliacytes, particularly microglia. In parallel with the delayed neuronal death, Tf-positive atrophied neurons and numerous ferritin-positive gliacytes appeared in the CA1 subfield of the hippocampus 4 days after ischemia, when glia fibrillary acidic protein (GFAP)-positive astrocytes also appeared throughout the hippocampal structure. A considerable number of ferritin-positive phagocytes (reactive microglia) appeared in the stratum pyramidale from the seventh day. Our data show clearly that the mobilization of Tf and ferritin-positive phagocytes are linked with the degeneration of neurons induced by cerebral ischemia. These events may suggest an activation of iron handling system under the postischemic condition.
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PMID:Activation of iron handling system within the gerbil hippocampus after cerebral ischemia. 883 41

Ischemia and reperfusion cause coronary vascular and myocardial injury, which may be due to leukocyte-mediated processes. Antileukocyte measures have reduced injury after brief reperfusion periods of 1-3 h, but there has been little information on whether benefits are apparent after longer periods of reperfusion. We examined the effect of pretreatment with a monoclonal antibody (R15.7) to the CD18 family of leukocyte adhesion molecules (beta2-integrins) in dogs exposed to regional coronary ischemia for 1 h of left anterior descending coronary artery ligation and then reperfused for 48 h. Coronary microvascular permeability was assessed in vivo by measurement of protein leak index (PLI), using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilators bradykinin (BK) and ADP and the endothelium-independent vasodilator nitroprusside. At 48 h of reperfusion in untreated dogs there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. These abnormalities were decreased, but not abolished, in the dogs treated with R15.7. Relaxation of rings from the ischemic/reperfused artery to BK and ADP were blunted in the untreated dogs. R15.7 resulted in improvement in some, but not all, indexes of relaxation in response to BK and ADP. Relaxation to nitroprusside was normal in ischemic/reperfused coronary rings from both treated and untreated dogs. Therefore, after 1 h of regional coronary ischemia and 48 h of reperfusion, coronary endothelial injury, which was manifested by increased coronary microvascular permeability and abnormalities in coronary endothelium-dependent relaxation, was reduced by pretreatment with the anti-CD18 integrin antibody R15.7.
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PMID:An antibody to leukocyte integrins attenuates coronary vascular injury due to ischemia and reperfusion in dogs. 912 17

Endothelial injury, manifest by increased protein leak and decreased endothelium-dependent relaxation, occurs during reperfusion after ischemia. Transforming growth factor-beta (TGF-beta) has been shown to improve endothelium-dependent relaxation and reduce infarct size after short periods (from 20 min to 4.5 h) of reperfusion even when administered 24 h before the ischemic period. However, whether this represents a transient delay in the process leading to endothelial injury or prevention of injury has not been clear. To examine this issue, we measured protein leak, an index of coronary microvascular permeability, and endothelium-dependent relaxation, a measure of coronary endothelial function, after brief (1-h) and lengthy (48-h) reperfusion periods in dogs treated 30 min before ischemia with TGF-beta (30 microg/kg, i.v.) and control dogs. The left anterior descending coronary artery (LAD) was ligated for 1 h followed by 1 h of reperfusion (n = 10) or 48 h of reperfusion (n = 12). Protein leak was assessed by a dual-isotope technique by using radiolabeled transferrin and erythrocytes, and endothelium-dependent relaxation was assessed in epicardial coronary rings by using adenosine diphosphate (ADP), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent dilator. In control animals, there was a marked increase in the protein leak index (PLI) in the infarct zone (8.3 +/- 1.4 in 1-h dogs, and 8.7 +/- 0.9 in 48-h dogs) compared with the nonischemic myocardium (3.1 +/- 0.8 at 1 h, and 3.8 +/- 0.9 at 48 h). In TGF-beta treated dogs, there was a marked improvement in PLI in the infarct zone in 1-h dogs (PLI, 4.1 +/- 1.1; p < 0.05; or a 50% reduction compared with untreated dogs). However, the 48-h dogs treated with TGF-beta failed to demonstrate an improvement in PLI (PLI, 8.5 +/- 0.9; p = NS). Endothelium-dependent relaxation was impaired in the LAD in control dogs, and treatment with TGF-beta failed to improve relaxation after 1 or 48 h of reperfusion. Microvascular permeability was increased and endothelium-dependent relaxation was decreased after ischemia at both 1 and 48 h of reperfusion. Pretreatment with TGF-beta reduced the increase in permeability at 1 h of reperfusion but not at 48 h.
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PMID:Prevention of coronary vascular abnormalities early in reperfusion with TGF-beta may not prevent late coronary vascular injury. 926 47

Reactive oxygen species (ROS) have been implicated in a variety of pathological processes. The generation of highly reactive oxygen metabolites is an integral feature of normal cellular metabolism (mitochondrial respiratory chain, phagocytosis, arachidonic acid metabolism, ovulation and fertilization), however their production can multiply during pathological circumstances. Free oxygen radicals act either on the extracellular matrix or directly upon cellular membranes themselves. The fundamental defense of the organism against ROS include scavenger enzymes (superoxide dismutase, catalase, glutathione peroxidase) and lipid- and water soluble antioxidant compound (ascorbic acid, glutathione, albumin, transferrin, etc.). Their role in ischemia-reperfusion models have now been comprehensively investigated and it has become clear that ROS is to be blamed for the bulk of post-ischemic injuries, hence the basis for newly established antioxidant therapy in such cases. Also more and more studies have concluded a pivotal role of ROS in degenerative and inflammatory conditions, post-radiation processes and aging. Therefore it seems as we are continuously shedding light on the crucial part played by these molecules regarding a wide range of pathologies, we are discovering new therapeutic windows that would clinically assist us in managing such conditions.
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PMID:Oxygen free radicals and their clinical implications. 940 83


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